Salmon calcitonin oral absorption

Sinko PJ, Lee YH, Makhey V, Leesman GD, Sutyak JP, Yu H, Perry B, Smith CL, Hu P, Wagner EJ, Falzone LM, Mcwhorter LT, Gilligan JP and Stern W (1999) Biopharmaceutical Approaches for Developing and Assessing Oral Peptide Delivery Strategies and Systems In Vitro Permeability and In Vivo Oral Absorption of Salmon Calcitonin (Set). Pharm Res 16 pp 527-533. 

Shah, R.B., A. Palamakula, and M.A. Khan. 2004. Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin. J Pharm Sci 93 1070. 

Calcitonin is another compound that was often incorporated into nanoparticles to enhance its oral absorption. Takeuchi et al. (2001) developed Elcato-nin-loaded PLGA nanospheres coated with chitosan, observing a reduction of blood calcium level. Sakuma et al. (2002) hypothesizes that both mucoadhesion of nanoparticles incorporating salmon calcitonin into the GI mucosa (Sakuma et al. 1999,2002) and increase in the stability of salmon calcitonin in the GI tract (Sakuma et al. 1997) result in the improvement of salmon calcitonin absorption. Moreover, chitosan-PEG nanocapsules increased the absorption of salmon calcitonin (Prego et al. 2006). 

Another approach to enzyme inhibition is to manipulate the pH to inactivate local digestive enzymes. Lee et al. conducted studies demonstrating that oral absorption properties of salmon calcitonin can be modulated by changing intestinal pH. Reducing the intestinal pH in the GI tract, increased absorption of the intact peptide.34 A sufficient amount of a pH-lowering buffer that lowers local intestinal pH to values below 4.5 can deactivate trypsin, chymotrypsin, and elastase. 

Sakuma, S., Suzuki, N., Kikuchi, H., Hiwatari, K. I., Arikawa, K., Kishida, A. and Akashi, M., Absorption enhancement of orally administered salmon calcitonin by polystyrene nanoparticles having poly(V-isopropylacrylamide) branches on their surfaces, Int. J. Pharm., 158, 69-78 (1997). 

Research on oral liposomal delivery systems has moved forward with the development of polymer-modified liposomes. For example, targeted PEGylated liposomes furnished with folic acid for oral delivery were promising, showing enhanced permeability of dextran (used as a marker) across Caco-2 cell monolayers (Anderson et al., 1999). PEG and chitosan-coated lipid nanoparticles were constmcted as oral delivery systems for salmon calcitonin (sCT). The PEG-coated nanoparticles did not alter the transepithelial electrical resistance of Caco-2 cell monolayers, while the chitosan-coated nanoparticles showed a dose-dependent increase in the permeability of dextran across the monolayers (Garcia-Fuentes et al., 2005). It demonstrated that the favourable interaction of the chitosan-coated nanoparticles with intestinal mucosa, together with their permeation enhancing characteristics, could improve the oral absorption of sCT. 

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